1. Field of the Invention
The invention relates to a process, and the intermediates useful in such a process, for the preparation of decahydro-8H-isoquino[2,1-g][1,6]naphthyridine derivatives, as a single enantiomer or mixture of enantiomers. Such compounds exhibit selective .alpha..sub.2 -blockade in mammals, and are therefore useful as medicaments for the treatment of physiological conditions affected by such selective blockade.
2Previous Disclosures
Processes for the preparation of various decahydro-8H-isoquino[2,1-g][1,6]naphthyridine derivatives, as a single enantiomer or mixture of enantiomers, were disclosed in U.S. patent application Ser. Nos. 174,750 and 257,372, and U.S. Pat. application Ser. No. 037,320 now issued as U.S. Pat. No. 4,791,108. The processes disclosed therein for the preparation of compounds of formula (I) utilize a common intermediate of formula: ##STR3##
The intermediate of formula (4) is obtained as an oily, amorphous solid which is difficult to isolate or purify by recrystallization; purification requires the extra steps of conversion to its hydrochloride salt, recrystallization of the salt, and conversion back to the free base for the next reaction. In contrast the present process affords an intermediate of formula (3) (shown infra) which is highly crystalline, and is thus easily isolated, purified and manipulated on a large scale.
Surprisingly, it has also been found that reduction of the --C.dbd.O group seen at the 8-position of a compound of formula (3) to --CH.sub.2 can be accomplished without concomitant reduction of other reactive sites of the molecule (in particular the 12-sulfonyl group and the 12-aminocarbonyl group), giving a compound of formula (I) in substantially pure form.